The mechanisms that could explain the outcome of HCV infection most likely occur in the early phase of infection but few studies have been able to assess large number of patients especially due to the limiting fact that most patients are absent of symptoms during this period. The Brazilian National Reference Laboratory for Viral Hepatitis, Fiocruz, Rio de Janeiro, Brazil has identified at least 46 cases of acute HCV infection before 1999 and in the year 2001 initiated a pilot study that documented 34 cases in a four-year period. To provide clinical, laboratory and virological data along with specimens for immune response studies on HCV infection on a larger scale we propose to establish a large cohort of individuals with symptomatic and non-symptomatic acute HCV infection. The role of household and sexual transmission in acute HCV infection and possible covariate factors that may influence outcome of disease will be additionally investigated. The proposed study will focus on identifying two different groups of individuals with acute HCV infection, symptomatic and non-symptomatic, both diagnosed at the Hepatitis Clinic/Fiocruz, Rio de Janeiro, Brazil. Symptomatic subjects will be recruited following an accelerated screening algorithm at the clinic and the non-symptomatic mainly through a surveillance program specially designed for health professionals with needle stick injuries. Sequential blood draws will be implemented at specific time points to obtain PBMC and plasma for complementary studies that will analyze prospectively a variety of immune responses required to resolve infection and the viral evolution in subjects that progress to chronic infection. A detailed epidemiological questionnaire will be designed and administered to study subjects and to infected partners or household members who will donate blood samples to assess phylogenetic similarity between the infected HCV strains.